CVD-REAL 3: Renal benefits of SGLT2 inhibitors confirmed in real-world study
medwireNews: Patients with type 2 diabetes who are treated with sodium-glucose cotransporter (SGLT)2 inhibitors in routine clinical practice have a lower rate of kidney function decline and a reduced risk for adverse renal events compared with those given other glucose-lowering drugs, researchers report.
“These data suggest that the benefits of SGLT2 inhibitors on kidney function identified in clinical trials seem to be largely generalisable to clinical practice,” say Hiddo Heerspink, from the University Medical Center in Groningen, the Netherlands, and CVD-REAL 3 co-investigators.
The real-world study involved 65,231 patients from Israel, Italy, Japan, Taiwan, and the UK who initiated treatment for type 2 diabetes between 2013 and 2018. After propensity score matching there were 35,561 occurrences of SGLT2 inhibitor initiation – most commonly dapagliflozin (accounting for 57.9% of time spent on treatment), empagliflozin (34.1%), or canagliflozin (5.7%) – and 35,561 occurrences of treatment initiation with other glucose-lowering drugs, mainly dipeptidyl peptidase-4 inhibitors (23.1%) or insulin (18.4%).
Over an average follow-up of 14.9 months, the mean estimated glomerular filtration rate (eGFR) improved by 0.46 mL/min per 1.73 m² annually among patients treated with SGLT2 inhibitors, compared with a decline of 1.21 mL/min per 1.73 m² for those given other agents, from baseline rates of 90.6 and 90.9 mL/min per 1.73 m², respectively.
These findings translate into an adjusted average between-group difference in the annual rate of eGFR decline of 1.53 mL/min per 1.73 m² favoring SGLT2 inhibitors, report Heerspink and team in The Lancet Diabetes & Endocrinology.
SGLT2 inhibitor use was also associated with a significant 51% lower relative risk for the composite endpoint of a 50% decline in eGFR or end-stage kidney disease, with rates of 3.0 and 6.3 per 10,000 person–years for the SGLT2 inhibitor and control arms, respectively.
These results “complement findings from randomised trials” and were consistent in subgroup analyses by country, baseline eGFR, and concomitant medication use, say the researchers.
Writing in an accompanying comment, Paola Fioretto, from the University of Padua in Italy, and colleagues point out that “[i]mportantly, these results were seen in a population that was predominantly in primary prevention,” with just 8.3% of patients having an eGFR of 60 mL/min per 1.73 m² or lower.
The commentators note that the study had some limitations including a “relatively short” duration of follow-up and lack of data on urinary albumin-to-creatinine ratio (UACR).
Moreover, because the majority of patients in CVD-REAL 3 had normal eGFR at baseline, “it is difficult to conclude whether the results of CREDENCE in patients with reduced eGFR are applicable to routine clinical practice,” they add.
Nevertheless, Fioretto and co-authors conclude: “Although further […] studies with longer follow-up, a wide range of baseline renal function, and UACR data, are needed, the results of this important study, along with those of large-scale randomised trials, support the concept that SGLT2 inhibitors are effective in preventing the onset and progression of diabetic kidney disease.”
They believe that “in view of the absence of early predictors for [diabetic kidney disease], treatment with SGLT2 inhibitors could be considered for most, if not all, patients with type 2 diabetes.”
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